Abstract This work describes a pharmacological screening of Brazilian medicinal plants through their anti-inflammatory and cytotoxicity activities. Cytotoxicity activity of Mouriri elliptica and Alchornea glandulosa as well as the drugs celecoxib and doxorubicin were evaluated in cultures of peritoneal macrophages. The immune system influence of these samples was analyzed by determining production/inhibition of NO, production of tumor necrosis factor-α and production of interleukin-10. Regarding the production/inhibition of NO, there was NO production by M. elliptica and NO inhibition when the cells were exposed to A. glandulosa; Macrophages generally produce more NO, plus TNF-α and less IL-10, when associated to the tumor phenomenon, characterizing the inflammation involved in cancer. A. glandulosa showed anti-inflammatory effect, inhibited NO production and it was associated with low TNF-α production, although not as low as the macrophages associated with celecoxib and doxorubicin. These cytokines were not different in animals with tumor. Celecoxib confirms its anti-inflammatory action by markedly inhibiting NO and TNF-α, but also inhibiting IL-10 which is an anti-inflammatory cytokine. Doxorubicin inhibited NO in a higher percentage in the group of animals with tumor, although the literature reports that this drug stimulates the production of NO and this collaborates with its cytotoxic effect.

The endophytic fungus Microsphaeropsis arundinis was isolated from the capitula of the tropical plant Paepalanthus planifolius (Eriocaulaceae). The fungus was cultivated in seven different media, and the ethyl acetate extracts were tested against tumor cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay. The culture was scaled up using parboiled rice medium, and the crude extract was purified by classical chromatographic analyses, leading to the isolation of seven compounds. The seven compounds isolated from the culture media included a new aromatic polyketide (1) and other known metabolites. The structures of all the compounds were elucidated by 1D and 2D nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS) analyses. An evaluation of the cytotoxicity of all the isolated compounds showed that these compounds exhibit less activity in comparison with the extract cultured in parboiled rice.

The halide-bridge cleavage reaction of the [Pd(C2 ,N-bzox)(µ-Cl)]2 compound (bzox = benzaldehydeoxime) with ethylenethiourea (L) in the 1:2 molar ratio at room temperature yielded the cyclopalladated compound [Pd(C2 ,N-bzox)(Cl)(L)] (1) whose replacement of the halide group by the addition of suitable salts afforded compounds of general formulae [Pd(C2 ,N-bzox)(X)(L)] {X = Br- (2), I- (3)}. All compounds were characterized by melting point, elemental analyses, infrared and 1H- and 13C{1H}-NMR spectroscopies revealing the complexes formation with the oxime coordinated to Pd(II) as C,N-chelating and the ethylenethiourea as a monodentate ligand via the sulfur atom. The cytotoxicity of cyclopalladated compounds has been evaluated in vitro against murine mammary tumor cell (LM3) showing cytotoxic activity similar to cisplatin.

Os efeitos dos compostos isolados de líquens brasileiros e seus derivados na produção de NO e H2O2 foram estudados utilizando macrófagos murinos na tentativa de desvendar suas possíveis propriedades imunomodulatórias. A citotoxicidade dos compostos foi estudada utilizando o ensaio de MTT. A estimulação dos macrófagos foi avaliada através da determinação de NO (metodologia de Griess) e H2O2 (peroxidase de raíz forte/vermelho de fenol) no sobrenadante de culturas de macrófagos peritoneais de camundongos Swiss. Este estudo demonstrou atividade estimulante de alguns compostos fenólicos e seus derivados na produção de NO e H2O2. A relação estrutura atividade sugere inúmeras direções sintéticas para futuros melhoramentos da atividade imunológica.

The effects of isolated compounds from Brazilian lichens and their derivatives on H2O2 and NO production were studied using murine macrophages as a part of an attempt to understand their possible immunomodulatory properties. The compound cytotoxicity was studied using MTT assay. Macrophage stimulation was evaluated by the determination of NO (Griess assay) and H2O2 (horseradish peroxidase/phenol red) in supernatants of peritoneal macrophage cultures of Swiss mice. This research demonstrated stimulatory activities of some phenolic compounds isolated from lichens and their derivatives on H2O2 and NO production. Structure-activity relationships suggest several synthetic directions for further improvement of immunological activity.

Os complexos polinucleares [{PdCl2(µ-Htrz)}n] (1) e [{PdBr2(µ-Htrz)}n] (2) (Htrz = 1,2,4-triazol) foram sintetizados neste trabalho. O composto 1 foi preparado a partir da substituição da acetonitrila do precursor [PdCl2(MeCN)2] pelo 1,2,4-triazol. A adição posterior de brometo de potássio ao meio reacional resultou na formação do complexo 2. Os complexos inéditos foram isolados, purificados e caracterizados por análise elementar, espectroscopias vibracional no infravermelho e eletrônica no UV-visível e curvas de análise termogravimétrica (TG). Os resultados experimentais sugerem que, em ambos os casos, a coordenação do 1,2,4-Htrz ocorra via átomos N(2) e N(4), atuando como pontes entre centros de paládio. O poliedro de coordenação quadrado-planar ao redor do paládio(II) é determinado pelos dois átomos de N do heterociclo e por dois ligantes cloro (1) ou bromo (2), em uma provável configuração trans. As curvas TG indicaram que a natureza do ligante aniônico não afeta significativamente a estabilidade térmica de 1 e 2. Os produtos finais de decomposição térmica foram identificados como paládio metálico pela técnica de difratometria de raios X de pó. Testes preliminares envolvendo a avaliação dos efeitos dos compostos 1, 2 e Htrz na produção de H2O2 e NO em culturas de macrófagos peritoneais de camundongos BALB/c foram realizados in vitro.

The 1,2,4-triazolyl-bridged polynuclear complexes [{PdCl2(µ-Htrz)}n] (1) and [{PdBr2(µ-Htrz)}n] (2) have been obtained in this work. Compound 1 is prepared by the displacement of acetonitrile from [PdCl2(MeCN)2] by 1,2,4-triazole (Htrz). Further addition of potassium bromide to the reaction medium afforded complex 2. The new complexes have been isolated, purified and characterized by means of elemental analysis, IR and UV-visible electronic spectroscopies and thermogravimetric (TG) curves. The experimental data suggested that, in both cases, the coordination of 1,2,4-Htrz takes place through the N(2) and N(4) atoms, bridging the palladium centers. The square-planar coordination polyhedron of palladium(II) is determined by two nitrogen atoms from the triazole ligands, while the other two coordination positions are occupied by the chloro (1) or bromo (2) ligands. TG curves indicated that the nature of the anionic ligand does not affect significantly the thermal stability of 1 and 2. The final products of the thermal decompositions were identified as metallic palladium by X-ray powder diffractometry. Preliminary tests involving the evaluation of the effects of compounds 1, 2 and Htrz on H2O2 and NO production in cultures of peritoneal macrophages from BALB/c mice were carried out in vitro.

Os ciclometalados de paládio(II) são compostos inorgânicos reativos empregados em vários estudos biológicos devido a seu potencial antitumoral e interação com o sistema imune. Neste estudo, a resposta imune e citotóxica induzida por dois complexos organopaladados: [{Pd(N,C-dmba)}2(µ-NCS)2 ] (1), [Pd(C-dmba)(NCS)(dppp)] (2) [dmba = N,N'dimetilbenzilamina, dppp = 1,3-bis(difenilfosfino)propano] e cisplatina (cis-DDP), como padrão, foram investigados em camundongos portadores do tumor ascítico de Ehrlich. Os camundongos foram divididos em cinco grupos e inoculados com (1) ou (2) ou cis-DDP ou apenas veículo ou solução salina tamponada de fosfatos (PBS). Diversos parâmetros foram avaliados, tais como a porcentagem de células tumorais presentes no exsudato peritoneal, os níveis de óxido nítrico (NO) e fator de necrose tumoral (TNF-alfa) séricos e o aumento na expectativa de vida. Os dados obtidos demonstram que o composto (2) apresentou atividade similar à da cis-DDP, como, por exemplo, aumento na expectativa de vida, diminuição dos níveis séricos de TNF-alfa e aumento da produção de NO.

Cyclometallated palladium(II) complexes are reactive inorganic compounds employed in several biological studies because of their antitumour potential and interaction with immune system. In the present study, the immune and citotoxic response induced by two organopalladated complexes: [{Pd(N,C-dmba)}2(µ-NCS)2 ] (1), [Pd(C-dmba)(NCS)(dppp)] (2) [dmba = N,N'dimethylbenzylamine, dppp = 1,3-bis(diphenylphosphino)propane] and cisplatin (cis-DDP), as standard, were investigated in mice bearing Ehrlich ascites tumour. The mice were divided into five groups and inoculated with the compounds (1) or (2) or cisplatin, or only vehicle or phosphate-buffered saline (PBS). Many parameters were evaluated, such as tumour cell percentage in the peritoneal exsudate, levels of seric nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) and increase in life span. Analysis of all data revealed, for compound (2), an activity similar to that presented by cisplatin, resulting in increased life span, lower levels of seric TNF-alpha and increase in NO production.

OBJECTIVE: To assess the effect of a new feed soy product fermented by Enterococcus faecium and Lactobacillus jugurti on the serum lipid levels of rabbits with induced hypercholesterolemia. METHODS: Thirty-two rabbits were divided into 4 groups as follows: 1) control (C); 2) hypercholesterolemic (H); 3) hypercholesterolemic + fermented product (HPF); and 4) control + fermented product (CPF). The H and HPF groups were fed with a diet with 0.15% (p/p) cholesterol in the first 15 days. C and CPF groups received regular food preparation. The HPF and CPF groups received 10 mL daily of the fermented 30 days. Blood samples were drawn at the beginning of the study and at the 15th and 30th days. Concentrations of total cholesterol, HDL-cholesterol, and triglycerides were analyzed. RESULTS: After 15 days, the HPF group showed a total cholesterol concentration lower (18.4%) than that of the H group (p=0.05), but this difference disappeared after 30 days. No change was observed in total cholesterol levels of C and CPF groups. After 15 days, the HDL-cholesterol was higher (17.8%) in the HPF group, but the triglyceride levels remained unchanged in all groups during the same period of time. CONCLUSION: The soy fermented product caused an 18.4% reduction in total cholesterol and a 17.8% increase in the HDL-fraction. It may, therefore, be a possible coadjutor in the treatment of hypercholesterolemia.